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Biophysicist in Profile

Gail Robertson

Gail Robertson

February 2022 // 2724

Gail Robertson grew up in the small town of Libby, Montana. She recalls, “My family lived there until I was 11, when, driven by upward mobility and my parents’ wish for a better future for the kids, we moved to a city where the kids could work a job, live at home, and pay tuition to an excellent state university, preferably graduating as engineers. Hence, we lived first in St. Paul, Minnesota, where my three older siblings graduated from ‘The U,’ and then in Williamsville, New York, where I finished high school and went to SUNY Buffalo. I know my parents were right to promote our education, but my longing for the profound natural beauty of Montana has never abated.

Gail Robertson, Kellett Professor in the Department of Neuroscience at the University of Wisconsin-Madison and incoming Biophysical Society President, started university as an English major, pursuing her love of poetry. She quickly found that “there was an entire world in the countless courses offered and, in the ‘70s, very few requirements. While attending a weekly Neurobiology Colloquium with eight other students in my sophomore year, reading Hodgkin and Huxley and other classics of neurophysiology, I realized I wanted to be an academic research scientist directing my own laboratory,” she shares. “I never wavered from that goal.”

She attended Washington University for her graduate education, where she studied under “the indefatigable Paul S.G. Stein, who is now in his 51st year teaching his legendary physiology course to 300+ undergraduates! He was an attentive and dedicated mentor, despite raising two small children on his own,” she says. “In my studies I inferred the organization of central pattern generators underlying rhythmic limb movements by resolving the synaptic drive recorded with microelectrodes in motor neurons innervating the limb musculature. I often wondered about the mechanisms coordinating the expression of multiple ion channel types and the resulting firing patterns of the motor neuron.”

She made the fortuitous decision in graduate school to take Physical Chemistry and the Membrane Biophysics course offered by Paul De Weer, Luis Reuss, and the late Bob Rakowski. “I felt at sea in the Membrane Biophysics class of 20, the only woman, and intimidated by the aggressive Socratic method that was the order of the day, but I ultimately excelled,” Robertson notes. “I did not realize at the time that I would later, as an assistant professor, put those principles into action, characterizing the biophysical behavior of recently cloned channels. Despite my lack of formal training in a biophysics lab, the experience in that Membrane Biophysics course was crucial in providing the kernel of confidence I would need to tackle those projects as I set out on my own.”

Following completion of her PhD and based on her interest in the control of membrane conductances underlying complex behaviors, she was encouraged by a faculty member at Washington University to consider the emerging field of neurogenetics. Though she knew nothing of genetics, she was intrigued and joined the lab of Barry Ganetzky at the University of Wisconsin. “In the first lab meetings I felt I’d been dropped in a foreign country where no one spoke my language. For a time, I was the resident electrophysiologist in the lab, characterizing mutant phenotypes in various Drosophila preparations and learning how to set up genetic crosses,” she explains. “But mostly I received amazing training in molecular biology, ‘walking’ hundreds of kilobases along the chromosome and screening cDNA libraries homemade from tens of thousands of fly heads. These efforts led to cloning the gene slowpoke (slo), encoding the first BK potassium channel.”

“Another gene that emerged from the Ganetzky enterprise was ether-a-go-go and a related gene, hERG, cloned from human hippocampus. As an independent assistant professor, I decided to figure out the physiological function of the hERG gene, expressing it in Xenopus oocytes and then comparing the biophysical and pharmacological properties to native currents reported in the literature. This work was done together with Matt Trudeau, my first graduate student and now a professor at the University of Maryland School of Medicine,” she says. “We found that hERG encoded the channels underlying IKr, a repolarizing current in the heart and the target of acquired long QT syndrome. Craig January, Zhengfeng Zhou (now at Oregon Health & Science University), and I created a technology readily adopted by the pharmaceutical industry to counter-screen drugs in development for risk of the catastrophic arrhythmias associated with acquired long QT syndrome. Much of the rest of my career has focused on the hERG channel, although drug safety remains just one aspect of our research.”

Inspired by the work of Carol Deutsch showing cotranslational association of ion channel subunits, Robertson’s then-graduate student Pallavi Phartiyal made the discovery that alternate transcripts encoding two subunits of the hERG channel, hERG1a and 1b, must be near or interacting with each other during channel biogenesis. “Finding no evidence in the literature at the time of such interactions in any biological system, we published but then shelved further work on the project. Ten years later, we found these transcripts were also coregulated by shRNAs specifically targeting either transcript. This set us on course to show they interact cotranslationally, both in heterologous systems and in cardiomyocytes. Employing RNA-IP and single-molecule fluorescence in situ hybridization, we made the further surprising observation that mRNAs encoding different ion channels, such as those engaged in producing the ventricular action potential, are also associated and coregulated,” she says. “These observations have led us closer to a major question dogging me throughout my career: How is the balance of different ion channels achieved to create a ventricular action potential, or the synaptic drive underlying coordinated movements? Ongoing efforts in the lab are focused on understanding the mechanisms by which channel mRNAs are associated and quantitatively translated as an ensemble.”

One of the biggest challenges in Robertson’s career has been learning mentoring skills without formal training, which is much more common now than in years past. Mentoring has also come to be the most rewarding aspect of her work. “The mentoring works in both directions: I am especially grateful to the members of my lab, the most culturally diverse group of my career. We have made events surrounding the Black Lives Matter movement an ongoing topic of lab discussion, and my trainees have elevated our collective aspirations for a diverse Biophysical Society through activities such as Black in Biophysics, founded by my graduate student Whitney Stevens-Sostre,” Robertson shares. “The folks in my lab come from six countries and Puerto Rico, and each has a unique perspective. Those perspectives are, of course, also essential to creative and forward-thinking science, which is challenging and requires all the talent we can foster. I love my trainees and staff, and I tell them so. They return my regard by working hard, pushing new discoveries, and training the next generation of scientists coming into the lab.”

The Biophysical Society was the first place Robertson saw women engaged in science and holding leadership positions. “I had the opportunity to serve on Council early in my career, and that revealed to me some of the structural problems holding women back. I’ll never forget Dorothy Beckett’s brave indifference to the eye rolls in the room as she insisted it was possible and indeed essential to find highly qualified women to speak in symposia. That was leadership,” she says. “We continue to have these discussions today, exercising vigilance in supporting women and other underrepresented groups in our society. I feel that most BPS members support these efforts that make the Society a welcoming place.”

“For me, like many members of the Biophysical Society, the Annual Meeting has an outsized impact on scientific life. It spurs us to complete and craft our best stories for presentations, offers each year a new world of advances, and builds a community among scientists that makes us all better. I treasure those relationships that get renewed and strengthened each year. The committees and Subgroups, run by volunteer members, are powerful drivers for the Society. And now more than ever I appreciate the BPS staff, who do much more than I realized prior to becoming president-elect. I used to think no one could fill [former Executive Officer] Ro Kampman’s shoes, but Executive Officer Jennifer Pesanelli has taken the Society in many new directions and has guided her staff and the BPS leadership team with calm and grace through the previously unimaginable challenges of the pandemic. Finally, with three journals (Biophysical Journal, Biophysical Reports, and The Biophysicist) each under fresh editorial leadership, I am excited about our renewed potential as a Society to promote scientific excellence and support the next generation of biophysicists.”